ObjectiveTo investigate the mechanism by which Luoshi Neiyi prescription treats endometriosis （EMs） through the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway. MethodsAnimal experiments were conducted with 50 female SD rats， which were randomized into a sham operation group （10 rats） and a modeling group （40 rats）. An autologous endometrial transplantation method was used for the modeling of EMs. The 36 successfully modeled rats were randomly allocated into four groups （n=9 each）： The model group， the low-dose （7.87 g·kg^-1） Luoshi Neiyi prescription group， the high-dose （15.74 g·kg^-1） Luoshi Neiyi prescription group， and the dienogest （0.20 mg·kg^-1） group. The physiological status and ectopic lesion volumes of rats in each group were observed. Hematoxylin-eosin （HE） staining was used to observe the morphology of the eutopic endometrial tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of inflammatory factors including interleukin-1β （IL-1β） and prostaglandin E₂ （PGE₂） in the serum of EMs rats. Immunohistochemistry was used to detect the expression of matrix metalloproteinase-9 （MMP-9） and vascular endothelial growth factor A （VEGFA） in the eutopic endometrial tissue. Western blot was adopted to determine the protein levels of TLR4， myeloid differentiation factor 88 （MyD88）， phosphorylated nuclear factor-κB （p-NF-κB）/NF-κB， MMP-9， and VEGFA in the eutopic endometrial tissue. In the cell experiments， the cell-counting kit-8 （CCK-8） assay was employed to screen the optimal concentration of Luoshi Neiyi prescription-containing serum， and a scratch assay was performed to assess the migration ability of iheESCs cells. Interventions with Luoshi Neiyi prescription-containing serum， resatorvid （TAK-242， a TLR4 inhibitor）， and lipopolysaccharides （LPS， a TLR4 agonist） were conducted， and Western blot was used to detect the expression of proteins related to the TLR4/NF-κB signaling pathway. ResultsThis experiment successfully replicated 36 EMs rat models. Compared with the sham operation group， the model group exhibited visible ectopic lesions on the abdominal wall and an increase in the writhing response score （P<0.01）. Furthermore， HE staining revealed the model group exhibited a thickened eutopic epithelium， stromal cell disarrangement， and evident infiltration of inflammatory cells. In addition， the model group showed elevated serum levels of IL-1β and PGE₂ （P<0.05， P<0.01）， increased positive expression of MMP-9 and VEGFA in the ectopic endometrial tissue （P<0.01）， and up-regulated protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01）. Compared with the model group， all treatment groups exhibited a reduction in the ectopic lesion volume （P<0.01）. Furthermore， the writhing response scores were decreased in the high-dose Luoshi Neiyi prescription group and the dienogest group （P<0.05， P<0.01）. The pathological state of the ectopic endometrial tissue was alleviated to varying degrees in the treatment groups. Low-dose Luoshi Neiyi prescription reduced serum PGE₂ levels， and high-dose Luoshi Neiyi prescription and dienogest decreased serum IL-1β and PGE₂ levels in EMs rats （P<0.05， P<0.01）. The treatment groups showed decreased positive expression of MMP-9 and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01） and down-regulated protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01）. The cell experiments showed that 5%， 10%， and 20% Luoshi Neiyi prescription-containing sera significantly reduced the viability and inhibited the migration of iheESCs. Compared with the control group， 5%， 10%， and 20% Luoshi Neiyi prescription-containing serum groups and the TAK-242 group showed reduced protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA （P<0.01）. Compared with the control group， the LPS group showed increased expression of the above proteins （P<0.01）. Compared with the LPS group， the LPS+5%， 10%， and 20% Luoshi Neiyi prescription-containing serum groups showed reduced expression of the above proteins （P<0.05， P<0.01）. ConclusionLuoshi Neiyi prescription may modulate the TLR4/NF-κB signaling pathway to reduce the inflammatory response and histopathological damage in the eutopic endometrium and suppress the adhesive， invasive， and angiogenic biological processes in the ectopic endometrial tissue， thereby exerting its therapeutic effect on EMs.

Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern to activate the stimulator of interferon genes (STING) signaling in macrophages, promoting tissue inflammation. However, its role in acute myocardial infarction (AMI) remains unclear. Macrophage-specific Sting1 knockout mice were used to validate STING's pathological role in AMI. Cardiac and liver mtDNA were used to activate macrophages in co-culture systems with cardiomyocytes to assess fibrosis and hypertrophy. Panaxatriol saponin (PTS) was tested for its ability to block mtDNA-driven macrophage activation and subsequent cardiomyocyte damage. STING-PTS binding ability was analyzed. AMI rats received PTS to evaluate its effects on myocardial inflammation and ventricular remodeling. In vivo, macrophage-specific Sting1 knockout reduced myocardial inflammation and injury after AMI. In vitro, mtDNA-activated macrophages induced cardiomyocyte fibrosis and hypertrophy through STING signaling. PTS suppressed mtDNA-driven macrophage activation by directly binding STING, thereby blocking inflammatory cascades. In AMI rats, PTS treatment attenuated acute inflammation and reversed ventricular remodeling. These findings establish the mtDNA-STING axis in macrophages as a critical driver of post-AMI inflammation and identify pharmacological STING inhibition with PTS as a promising therapeutic strategy. The study bridges genetic validation with translational applications, highlighting macrophage STING as a novel target for ischemic heart disease management.

OBJECTIVES: Stigma is common among community-dwelling patients with schizophrenia and has a profound negative impact on both psychiatric symptoms and quality of life. This study aims to explore the association between stigma and quality of life in this population and to examine the multiple mediating roles of anxiety and depression symptoms. METHODS: The multi-stage stratified cluster random sampling method was used to select the community-dwelling patients with schizophrenics in Chengdu, Sichuan Province, China. The questionnaire included general demographic characteristics, stigma question, the Generalized Anxiety Disorder-7 (GAD-7) scale, the Patient Health Questionnaire-9 (PHQ-9), and the 12-item Short Form Health Survey (SF-12). The SF-12 was used to measure quality of life, including physical health and mental health dimensions. A multiple mediation model was used to analyse the mediating effects of anxiety and depression symptoms together between stigma and quality of life. RESULTS: A total of 1 087 community patients with schizophrenia were included with a mean age of 50.68±12.73 years; 525 (48.30%) were male. Stigma was reported by 543 patients (49.95%). Anxiety symptoms were present in 292 patients (26.86%), and depression symptoms in 407 patients (37.44%). The physical health quality of life score was 72.01 ± 20.99, and the mental health quality of life score was 71.68 ± 19.38. Multiple mediation analysis showed that stigma directly affected quality of life, and also indirectly affected quality of life through anxiety and depression symptoms. Anxiety and depression jointly mediated 42.26% of the total effect of stigma on physical health quality of life and 47.51% on mental health quality of life. CONCLUSIONS Reducing stigma and preventing anxiety and depression symptoms in community-dwelling patients with schizophrenia can effectively improve their quality of life and support reintegration into society.
Humans ; Quality of Life ; Male ; Depression/psychology* ; Middle Aged ; Social Stigma ; Schizophrenia ; Female ; Anxiety/psychology* ; China ; Surveys and Questionnaires ; Adult ; Schizophrenic Psychology ; Independent Living ; Aged

Currently,there are practical and technical difficulties in the construction of clinical ques-tions in the development of clinical practice guidelines.Clinicians or guideline developers seldom construct clin-ical questions based the actual case scenario,leading to some information loss between structured and actual clinical connotation.To overcome this challenge,we proposed a case-guided questions construction approach,and carried out case research and verification in the formulation of the guideline.We found that this method could more efficiently and scientifically assist the formulation of clinical questions,and provide reference for clinicians or guideline developers.

Objective To explore the relationship between postoperative defecation dysfunction and quality of life in children with anorectal malformation(ARM)complicated with spinal cord anomalies(SCA)and analyze the impact of different types of SCA on ARM patients in order to provide a reference for the early clinical identification of high-risk children with poor prognosis.Methods A retrospective analysis was conducted on 282 ARM neonates admitted to our department between June 2015 and April 2021.Radiological examinations were applied to evaluate the development of the spinal cord,and Rintala score and the PedsQL 4.0 scale were employed to assess postoperative defecation function and quality of life,respectively.According to their SCA types and other complications,the patients were grouped.The relationship between these factors and defecation function as well as quality of life was then analyzed.Results Among the 282 subjected children,104(36.9%)had SCA.The incidence of SCA varied significantly across different types of ARM(P=0.002),with the highest incidence observed in vaginal fistula patients(100.0%)and the lowest in children without fistula(13.6%).Radiological findings revealed that sacral bone anomalies were common,with absent coccyx(62.7%)and vertebral anomalies(69.8%)being the most prevalent.The SCA group had significantly lower Rintala bowel function score(12.70±3.24)and PedsQL 4.0 quality of life score(81.42±5.03)than the non-SCA group(P<0.001).As the increment of SCA types,both the Rintala score and PedsQL 4.0 score were in a significant downward trend(P<0.001).Among the children with different types of SCA,those with tethered cord syndrome had the statistically lowest Rintala score(8.05±2.35,P<0.05).Meanwhile,their PedsQL 4.0 score(75.90±3.35)was significantly lower than those of other types except syrinx(P<0.05).Multiple linear regression analysis indicated that both SCA and sacral bone anomalies exerted notably negative impacts on the Rintala score and PedsQL 4.0 score(P≤0.001),with SCA having the most pronounced effect.Conclusion SCA is closely associated with postoperative defecation dysfunction and diminished quality of life in ARM children.The greater the type and number of SCAs,the worse the postoperative defecation function and quality of life.Early identification of concomitant SCAs holds significant clinical value for predicting postoperative outcomes in ARM patients.

Objective To analyze changes in sleep,mood state,and brain function in healthy populations living in near-sea-level environments before and after exposure to high-altitude environment,and to explore the correlations between regional brain functional changes and variations in sleep and mood states.Methods A total of 45 healthy volunteers were enrolled.The participants came from regions of near-sea-level altitudes and were exposed to the high-altitude environment for a short period of time.The Pittsburgh Sleep Quality Index(PSQI),Zung Self-Rating Depression Scale(SDS),Patient Health Questionnaire-9(PHQ-9),Zung Self-Rating Anxiety Scale(SAS),and Generalized Anxiety Disorder-7(GAD-7)were administered to assess sleep quality as well as depressive and anxiety symptoms at 4 time points—prior to high-altitude exposure,immediately after exposure,one month after returning to low-altitude regions,and three months after returning to low-altitude regions.Resting-state functional magnetic resonance imaging(rs-fMRI)data were collected before and after high-altitude exposure,and regional brain functional parameters,including the amplitude of low-frequency fluctuations(ALFF)and functional connectivity strength,were analyzed.Statistical analyses were performed,including a linear mixed-effects model to evaluate longitudinal changes in scale scores,paired-sample t-tests to compare brain function differences before and after exposure,and Pearson correlation analyses to examine the relationship between brain functional changes and alterations in sleep and mood states.Results Compared with the pre-exposure findings,the participants exhibited significantly increased PSQI scores(8.89±4.41 vs.5.08±2.69,P<0.05)and PHQ-9 scores(3.60±4.19 vs.1.54±2.30,P<0.05)immediately after high-altitude exposure.One month after returning to the low-altitude environment,both sleep and depression scores decreased relative to the findings immediately after exposure(PSQI:3.88±2.13 vs.8.89±4.41,P<0.05;PHQ-9:1.50±2.25 vs.3.60±4.19,P<0.05)and showed no statistically significant difference compared with the pre-exposure findings(P>0.05).Three months after returning to near-sea-level environment,sleep,depression,and anxiety scores were all reduced compared with the findings immediately after exposure(PSQI:3.76±2.31 vs.8.89±4.41,P<0.05;PHQ-9:1.24±2.13 vs.3.60±4.19,P<0.05;SAS:23.84±5.93 vs.27.93±7.05,P<0.05),also showing no significant difference compared with the pre-exposure levels(P>0.05).Brain function analysis revealed that,relative to the pre-exposure levels,ALFF in the bilateral superior temporal gyrus,insula,and dorsolateral prefrontal cortex(DLPFC)increased after high-altitude exposure(P<0.05),and that functional connectivity strength in the DLPFC was also elevated(P<0.05).Furthermore,changes in DLPFC functional connectivity strength were positively correlated with changes in sleep and mood scores(P<0.05).Conclusion High-altitude exposure has a significant impact on the sleep,mood states,and brain function of populations from near-sea-level regions,and DLPFC,in particular,is closely associated with changes in sleep and mood states.The findings of this study provide a theoretical basis for health management and intervention strategies in high-altitude environments.

Objective To summarize the best evidence for diaphragm rehabilitation in mechanically ven-tilated ICU patients with ventilator-associated diaphragm dysfunction based on evidence-based methods.Meth-ods A systematic search was conducted across guideline websites,professional associations,and Chinese/English databases for evidence regarding diaphragm rehabilitation in mechanically ventilated ICU patients.The search timeframe spanned from database inception to December 31,2024.Two researchers independently per-formed quality assessment and synthesized the evidence.Results Twenty articles were included:2 clinical de-cisions,1 guideline,2 evidence summaries,3 systematic reviews,7 randomized controlled trials(RCT),and 5 expert consensuses/opinions.Twenty-seven pieces of evidence were formed across 6 themes:rehabilitation team,rehabilitation assessment,rehabilitation interventions,outcome evaluation,precautions,and education/training.Conclusion This study summarizes the best evidence for diaphragm rehabilitation in ICU mechani-cally ventilated patients.Healthcare professionals should implement diaphragm rehabilitation by integrating this evidence with specific clinical contexts to improve patient outcomes and enhance nursing quality.

OBJECTIVE To explore the value of healthcare failure mode and effect analysis mode(HFMEA)com-bined with enhanced management of link quality in centralized processing of rigid endoscopic instruments.METHODS Totally 80 pieces of rigid endoscopic instruments that were recycled by the endoscopy room of otolar-yngology department of The First Medical Center of PLA General Hospital from Jan.2022 to Dec.2022 were as-signed as the control group,and 70 pieces of rigid endoscopic instruments that were recycled under the HFMEA model combined with enhanced management of link quality from Jan.2023 to Dec.2023 were assigned as the ex-perimental group.The effect of the management and the qualified rate of instruments were compared between the two groups of instruments,compare the satisfaction under the different intervention modes.RESULTS The scores of instrument disassembly and assembly,cleaning procedures,cleaning quality,environmental management and packaging quality were higher in the experimental group than in the control group(P＜0.05).The unqualified rate of instruments of the experimental group was 10.00％,lower than 23.75％of the control group(x2=4.926,P=0.026).The staff's satisfaction with the work of the experimental group was 91.67％,higher than 66.67％of the control group(Z=2.026,P=0.043).CONCLUSION For the centralized management of rigid endoscopic in-struments,the implementation of the enhanced management of link quality under the HFMEA mode can effective-ly improve the effect of management of the instruments and reduce the unqualified rate of recycled instruments,demonstrating a positive effect on raising the staff's satisfaction with the recycle process of instruments.

Objective:To investigate clinical characteristics, treatment approaches, and prognosis of drug-induced hypersensitivity syndrome (DIHS) in children.Methods:A retrospective analysis was performed on clinical data from pediatric inpatients with DIHS in Department of Dermatology, Beijing Children's Hospital from 2009 to 2023. The clinical data included demographic characteristics, clinical manifestations, laboratory findings, treatment regimens, and outcomes.Results:A total of 103 children with DIHS were included, comprising 54 males (52.4%) and 49 females (47.6%), with ages ( M [ Q1, Q3]) of 2.3 (1.2, 4.5) years. Primary causative drugs were antibiotics (52 cases, 45.2%), antiepileptic drugs (41 cases, 35.7%), and nonsteroidal anti-inflammatory drugs (19 cases, 16.5%), with a median latency period of 12 days. All patients presented with rashes, including 72 (69.9%) with maculopapular rashes, 69 (67.0%) with edema (including 46 with facial edema). Lip involvement occurred in 25 cases (24.3%), and mucosal involvement was noted in 11 cases (10.7%). Additionally, 102 (99.0%) patients had fever, and 79 (76.7%) presented with lymphadenectasis. Eosinophilia was present in 64 cases (62.1%). Among 84 patients tested for atypical lymphocytes, 51 (60.7%) showed elevated percentages of atypical lymphocytes. Liver involvement was noted in 94 cases (91.3%), followed by pulmonary involvement in 31 (30.1%), gastrointestinal symptoms in 25 (24.3%), cardiac involvement in 14 (13.6%), renal involvement in 10 (9.7%), and pancreatic involvement in 7 cases (6.8%). Among 82 patients tested for blood immunocytes, 49 (59.8%) showed decreased percentages of B lymphocytes, and 69 (84.1%) showed decreased percentages of natural killer cells. Of 88 patients tested for serum immunoglobulins, 40 (45.5%) showed decreased IgA levels. Among 20 patients tested for serum cytokines, 15 (75.0%), 15 (75.0%), 13 (65.0%), and 12 (60.0%) showed elevated levels of interleukin (IL) -5, IL-6, IL-10, and interferon-γ, respectively. All patients received systemic glucocorticoid therapy, among whom 86 additionally received intravenous immunoglobulin therapy, 4 received Janus kinase inhibitors, and 3 received dupilumab. Five patients died, 9 developed hemophagocytic lymphohistiocytosis, 6 developed bronchiolitis obliterans, and 5 experienced long-term immune-related sequelae. Conclusions:Among these children with DIHS, antibiotics were the most common causative drugs, and the latency period could be shorter than 2 weeks. In addition to the common involvement of the liver and lungs, gastrointestinal and cardiac impairments were relatively frequent, while renal involvement was rare. Immunological features included decreased percentages of B lymphocytes and natural killer cells, reduced IgA levels, and elevated levels of cytokines such as IL-5, IL-6, IL-10, and interferon-γ.

Objective To explore the facilitators and barriers of palliative care volunteering,and to provide references for further advancement of palliative care volunteering.Methods Purposeful sampling was used to select 12 volunteers from a palliative care ward in Hangzhou,Zhejiang Province,between April and September 2024.Semi-structured interviews were conducted,and directed content analysis was applied to organize and analyze the data,followed by theme analysis.Results Facilitators and barriers for volunteers' participation in palliative care volunteering were extracted.The 5 sub-themes of facilitators include motivating factors and perceived benefits,support and collaboration among volunteers,professional training and healthcare recognition,increased social awareness and public acceptance,and government support and institutional safeguards.The 5 sub-themes of barriers include limitations in individual capacity,challenges in collaboration with patients,families and healthcare workers,inadequate management and service mechanisms,uneven development of palliative care and insufficient public attention to psychological problems,and inadequate relevant laws and incentives.Conclusion There are more factors affecting the development of palliative care volunteering,and healthcare professionals should adopt targeted strategies to promote the active participation of volunteers in order to promote the sustainable development of palliative care volunteering.